Sanagi Tomomi, Sasaki Tetsuya, Nakagaki Keiko, Minamimoto Takafumi, Kohsaka Shinichi, Ichinohe Noritaka
Department of Ultrastructural Research, National Center of Neurology and Psychiatry, National Institute of Neuroscience, Kodaira, Japan.
Department of Functional Brain Imaging, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan.
Front Cell Neurosci. 2019 Jul 30;13:344. doi: 10.3389/fncel.2019.00344. eCollection 2019.
Autism spectrum disorder (ASD) is one of the most widespread neurodevelopmental disorders, characterized by impairment in social interactions, and restricted stereotyped behaviors. Using immunohistochemistry and positron emission tomography (PET), several studies have provided evidence of the existence of activated microglia in ASD patients. Recently, we developed an animal model of ASD using the new world monkey common marmoset () and demonstrated ASD-like social impairment after the administration of valproic acid (VPA). To characterize microglia in this marmoset model of ASD from early toddler to adult, morphological analyses of microglia in VPA marmosets and age-matched unexposed (UE) marmosets were performed using immunohistochemistry for microglia-specific markers, Iba1, and P2RY12. The most robust morphological difference between VPA marmosets and UE marmosets throughout the life span evaluated were the microglia processes in VPA marmosets being frequently segmented by thin and faintly Iba1-positive structures. The segmentation of microglial processes was only rarely observed in UE marmosets. This feature of segmentation of microglial processes in VPA marmosets can also be observed in images from previous studies on ASD conducted in humans and animal models. Apoptotic cells have been shown to have segmented processes. Therefore, our results might suggest that microglia in patients and animals with ASD symptoms could frequently be in the apoptotic phase with high turnover rates of microglia found in some pathological conditions.
自闭症谱系障碍（ASD）是最普遍的神经发育障碍之一，其特征为社交互动受损和刻板行为受限。多项研究利用免疫组织化学和正电子发射断层扫描（PET），证实了ASD患者体内存在活化的小胶质细胞。最近，我们利用新大陆猴普通狨猴建立了一种ASD动物模型，并证明在给予丙戊酸（VPA）后出现了类似ASD的社交障碍。为了从幼年早期到成年期对这种狨猴ASD模型中的小胶质细胞进行特征描述，我们使用针对小胶质细胞特异性标志物Iba1和P2RY12的免疫组织化学方法，对VPA处理的狨猴和年龄匹配未暴露（UE）的狨猴的小胶质细胞进行了形态学分析。在整个评估的生命周期中，VPA处理的狨猴和UE狨猴之间最显著的形态学差异是，VPA处理的狨猴的小胶质细胞突起经常被薄且微弱的Iba1阳性结构分割。在UE狨猴中很少观察到小胶质细胞突起的分割现象。在之前关于人类和动物模型ASD的研究图像中也可以观察到VPA处理的狨猴中小胶质细胞突起的这种分割特征。已显示凋亡细胞具有分割的突起。因此，我们的结果可能表明，患有ASD症状的患者和动物体内的小胶质细胞可能经常处于凋亡阶段，在某些病理条件下小胶质细胞的更新率很高。
